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| Status |
Public on Nov 01, 2023 |
| Title |
Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Despite the high prognostic value of immune infiltrates in colorectal cancer (CRC), metastatic disease remains resistant to immunotherapy by immune checkpoint blockade (ICB). Here we show in a metastatic CRC multi-tumor preclinical model that orthotopically-implanted primary colon tumors can spontaneously exert a colon-specific and immune-dependent antimetastatic effect on distant hepatic lesions. An immune signature, integrating antitumor CD8 T cells, dendritic cells and protumor macrophages, that we called MicroEnvironment (ME)-score, was predictive of the antimetastatic effect. ScRNA-Seq and phenotypic analyses revealed that enterotropic α4β7 integrin expressing tumor neoantigen-specific CD8 T cells were key components of the systemic immune response responsible for the antimetastatic effect. Accordingly, the presence of concomitant colon tumors improved the efficacy of proof-of-concept ICB on liver lesions and generated a protective memory immune response whereas antibody-mediated partial depletion of α4β7+ cells abrogated the control of metastatic disease by the primary tumor. Finally, in a metastatic CRC patients’ cohort, we show increased expression of genes encoding the α4β7 integrin and of the ME-score in ICB responsive metastases concomitant with increased proportions of circulating α4β7+ CD8 T cells. Our findings identify a systemic cancer immunosurveillance role for gut primed tumor-specific α4β7+ CD8 T cells.
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| Overall design |
Single-cell RNA sequencing was performed on sorted T cells from mice liver and colon tumors and blood samples, harvested at day 10 post tumor implantations (intra-hepatic (IH)+intra-colon (IC) concomitant injections (IH+IC group) or IH alone (al.) injections). Each sample corresponds to a pool of 18 (for IH+IC group) or 9 (for IH al. group) IH tumors; 18 (for IH+IC group) IC tumors; 18 (for IH+IC group) or 9 (for IH al. group) blood samples.
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| Contributor(s) |
Feliu V, Gomez-Roca C, Michelas M, Thébault N, Lauzeral-Vizcaino F, Salvioni A, Scandella L, Sarot E, Valle C, Balança C, Scarlata C, Delord J, Ayyoub M, Devaud C |
| Citation missing |
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| |
| Submission date |
Nov 30, 2022 |
| Last update date |
Nov 01, 2023 |
| Contact name |
Christel Devaud |
| E-mail(s) |
christel.devaud@inserm.fr
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| Organization name |
INSERM
|
| Department |
UMR1037
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| Lab |
CRCT - Team 1
|
| Street address |
2 Avenue Hubert Curien
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| City |
Toulouse |
| ZIP/Postal code |
31037 |
| Country |
France |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
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| GSM6767488 |
intrahepatic injection alone - Control - Liver |
| GSM6767489 |
intrahepatic injection alone - Control - Blood |
| GSM6767490 |
intracolorectal and intrahepatic injection - Sample 1 - Colon |
| GSM6767491 |
intracolorectal and intrahepatic injection - Sample 1 - Liver |
| GSM6767492 |
intracolorectal and intrahepatic injection - Sample 1 - Blood |
| GSM6767493 |
intracolorectal and intrahepatic injection - Sample 2 - Colon |
| GSM6767494 |
intracolorectal and intrahepatic injection - Sample 2 - Liver |
| GSM6767495 |
intracolorectal and intrahepatic injection - Sample 2 - Blood |
| GSM6767496 |
intrahepatic injection alone - Control - Liver - TCR |
| GSM6767497 |
intrahepatic injection alone - Control - Blood - TCR |
| GSM6767498 |
intracolorectal and intrahepatic injection - Sample 1 - Colon - TCR |
| GSM6767499 |
intracolorectal and intrahepatic injection - Sample 1 - Liver - TCR |
| GSM6767500 |
intracolorectal and intrahepatic injection - Sample 1 - Blood - TCR |
| GSM6767501 |
intracolorectal and intrahepatic injection - Sample 2 - Colon - TCR |
| GSM6767502 |
intracolorectal and intrahepatic injection - Sample 2 - Liver - TCR |
| GSM6767503 |
intracolorectal and intrahepatic injection - Sample 2 - Blood - TCR |
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| This SubSeries is part of SuperSeries: |
| GSE193594 |
Distant antimetastatic effect of enterotropic colon cancer-derived α4β7 CD8 T cells |
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| Relations |
| BioProject |
PRJNA907008 |
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